Transfusion of blood products has been shown to impact a number of the recipient immune responses. The immunological consequences of transfusion include the production of alloantibodies, increased incidence of bacterial infection, increased relapse rates for at least some kinds of tumors, transfusion-associated graft-versus-host disease, increased survival of organ allografts, induction of anti-leukemic responses and reversal of some cases of spontaneous recurrent abortions. Although donor blood and recipient have been matched for blood group antigens, they are not routinely typed for HLA antigens. Thus in almost all cases, the transfusion results in the introduction of alloantigens to the recipients. The goal of the studies is to define the mechanisms regulating recipient immune responses to alloantigen in order to understand how transfusion can influence immune responses and how to best regulate these responses. One approach to study the recipient responses to alloantigen is to study the responses which are responsible for the elimination of the allogeneic donor cells. Recipient CD8+ and B cells are responsible for the elimination of allogeneic donor cells in a murine model sytem. Optimal responses by these cells requires help from CD4+ cells. The most rapid recipient responses were in response to activated donor CD4+ cells acting as alloantigen presenting cells. The proposed experiments will examine the relative importance of this novel pathway by comparing the role of donor CD4+ cells and macrophages as antigen presenting cells. These donor cell populations will be compared by measuring the minimum number of each type of donor cell that is required for recipient immune responses, the interactions that are important in activation of recipient effector responses for each type of cell and how the immune responses generated by these cells regulate other immune responses.